Diphenyl sulphide

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Data is from peer-reviewed journal

Data source

Reference

Reference Type:

publication

Title:

Acute and Subacute oral toxicity of polychlorinated diphenyl sulfides in mice: determining LD50 and assessing the status of hepatic oxidative stress

Author:

XUESHENG ZHANG, FU LIU, BINYUAN CHEN, YING LI,y and ZUNYAO WANG

Year:

2012

Bibliographic source:

Environmental Toxicology and Chemistry, Vol. 31, No. 7, pp. 1485–1493, 2012

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

The objective of this study was to evaluate the subacute oral toxicity study of Diphenyl sulphide (CAS No.139-66-2) orally in female mice.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Diphenyl sulphide

EC Number:

205-371-4

EC Name:

Diphenyl sulphide

Cas Number:

139-66-2

Molecular formula:

C12H10S

IUPAC Name:

(phenylsulfanyl)benzene

Test material form:

liquid

Details on test material:

Name of test material (as cited in study report): Diphenyl sulphide
Molecular formula:C12H10S
Molecular weight:186.277 g/mol
Smiles : c1(Sc2ccccc2)ccccc1
InChI : 1S/C12H10S/c1-3-7-11(8-4-1)13-12-9-5-2-6-10-12/h1-10H
Substance Type: Organic
Physical State: Liquid

Specific details on test material used for the study:

- Name of test material (as cited in study report): Diphenyl sulfides (DSP)
- Molecular formula: C12-H10-S
- Molecular weight: 186.277 g/mole
- Substance type: Organic
- Physical state: No data available
- Impurities (identity and concentrations): < 1%

Test animals

Species:

mouse

Strain:

other: Kunming

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Qinglongshan Animal Breeding Center
- Age at study initiation: 5 weeks old
- Weight at study initiation: 18–20 g body wt
- Fasting period before study: Not reported
- Housing: Animals were caged in groups of 10 using dust-free poplar chips for bedding.
- Diet (e.g. ad libitum): Rodent chow, ad libitum
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.0 ± 1.0 degC
- Humidity (%):50–60%
- Air changes (per hr): 10 times/hr
- Photoperiod (hrs dark / hrs light): 12 h: 12 h light: dark cycle (8:00 AM–8:00 PM).

IN-LIFE DATES: From: To: No data available

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS: No data available

DIET PREPARATION
- Rate of preparation of diet (frequency): No data available
- Mixing appropriate amounts with (Type of food): No data available
- Storage temperature of food: No data available

VEHICLE
- Justification for use and choice of vehicle (if other than water): Considering the lower water solubility of Diphenyl sulfides, corn oil was selected as vehicle.
- Concentration in vehicle: 0, 1, 10 and 100 mg/kg/day
- Amount of vehicle (if gavage): 0.1–0.2 ml/100 g
- Lot/batch no. (if required): No data available
- Purity: No data available

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

28 days (4 weeks)

Frequency of treatment:

Daily

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 other: mg/kg/day

Doses / concentrations 2

Dose / conc.:

1 other: mg/kg/day

Doses / concentrations 3

Dose / conc.:

10 other: mg/kg/day

Doses / concentrations 4

Dose / conc.:

100 other: mg/kg/day

No. of animals per sex per dose:

Total: 40
0 mg/kg/day: 10 female
1 mg/kg/day: 10 female
10 mg/kg/day: 10 female
100 mg/kg/day: 10 female

Control animals:

yes, concurrent vehicle

Details on study design:

Details on study design
- Dose selection rationale: No data available
- Rationale for animal assignment (if not random): Randomly
- Rationale for selecting satellite groups: No data available
- Post-exposure recovery period in satellite groups: No data available
- Section schedule rationale (if not random): No data available

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: No data available
- Time schedule: No data available
- Cage side observations checked in table [No.?] were included. No data available

DETAILED CLINICAL OBSERVATIONS: No data available
- Time schedule: No data available

BODY WEIGHT: No data available
- Time schedule for examinations: No data available

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): No data available
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data available
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data available

FOOD EFFICIENCY: No data available
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data available

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data available
- Time schedule for examinations: No data available

OPHTHALMOSCOPIC EXAMINATION: No data available
- Time schedule for examinations: No data available
- Dose groups that were examined: No data available

HAEMATOLOGY: No data available
- Time schedule for collection of blood: No data available
- Anaesthetic used for blood collection: No data available
- Animals fasted: No data available
- How many animals: No data available
- Parameters checked in table [No.?] were examined. No data available

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: At the termination of study
- Animals fasted: No data available
- How many animals: All 40 animals were examined.
- Parameters checked in table [No.?] were examined. Superoxide dismutase (SOD) and malondialdehyde (MDA) were examined.

URINALYSIS: No data available
- Time schedule for collection of urine: No data available
- Metabolism cages used for collection of urine: No data available
- Animals fasted: No data available
- Parameters checked in table [No.?] were examined. No data available

NEUROBEHAVIOURAL EXAMINATION: No data available
- Time schedule for examinations: No data available
- Dose groups that were examined: No data available
- Battery of functions tested: sensory activity / grip strength / motor activity / other: No data available

OTHER: No data available

Sacrifice and pathology:

The mice were killed at the end of the experiment (28 d), and the livers were sampled and washed with normal saline.
HISTOPATHOLOGY: Yes

Other examinations:

No data available

Statistics:

Statistical analysis was performed by using SPSS Version 12.0 for Windows. The differences between the control and experimental groups were analyzed using one-way analysis of variance, and Tukey’s test. Values of p<0.05 were considered significant, and values of p<0.01 were accepted as having high statistical significance.

Results and discussion

Results of examinations

Clinical signs:

not specified

Mortality:

not specified

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

no effects observed

Description (incidence and severity):

Superoxide dismutase (SOD) activity was significantly decreased in 1, 10 and 100 mg/kg/day treated mice as compared to control.

Hepatic malondialdehyde (MDA) level in liver was significantly increased in 1, 10 and 100 mg/kg/day treated mice as compared to control.

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Effect levels

Key result

Dose descriptor:

NOAEL

Effect level:

100 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

female

Basis for effect level:

other: No significant effect were observed at this dose.

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

NOAEL was considered to be 100 mg/kg/day when Kunming female mice were treated with Diphenyl sulfides (DSP).

Executive summary:

In a Subacute oral toxicity study,Kunmingfemale mice were treated withDiphenyl sulfides (DSP) in the concentreation of 0, 1, 10 and 100 mg/kg/day orally by gavage.Superoxide dismutase (SOD) activity was significantly decreased andHepatic malondialdehyde (MDA) level in liver wassignificantly increased in 1, 10 and 100 mg/kg/day treated mice as compared to control. No significant effects were observed at the mortality, morbidity, clinical science, Food consumption, Hematology, gross and histopathology. Therefore, NOAEL was considered to be100 mg/kg/day whenKunmingfemale mice were treated withDiphenyl sulfides (DSP) orally for 28 days.